Intervertebral disc (IVD) injuries are a cause of degenerative changes in adults which can lead to back pain, a leading cause of disability. We developed a model of neonatal IVD regeneration with full functional restoration and investigate the cellular dynamics underlying this unique healing response. We employed genetic lineage tracing in mice using Scleraxis (Scx) and Sonic hedgehog (Shh) to fate-map annulus fibrosus (AF) and nucleus pulposus (NP) cells, respectively. Results indicate functional AF regeneration after severe herniation injury occurs in neonates and not adults. AF regeneration is mediated by Scx-lineage cells that lose ScxGFP expression and adopt a stem/progenitor phenotype (Sca-1, days 3-14), proliferate, and then redifferentiate towards type I collagen producing, ScxGFP+ annulocytes at day 56. Non Scx-lineage cells were also transiently observed during neonatal repair, including Shh-lineage cells, macrophages, and myofibroblasts; however, these populations were no longer detected by day 56 when annulocytes redifferentiate. Overall, repair did not occur in adults. These results identify an exciting cellular mechanism of neonatal AF regeneration that is predominantly driven by Scx-lineage annulocytes.

中文翻译：

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新生儿纤维环再生通过 Scleraxis 谱系细胞的募集和增殖发生。

椎间盘 (IVD) 损伤是成年人退行性变化的一个原因，可导致背痛，这是导致残疾的主要原因。我们开发了一种具有全功能恢复的新生儿 IVD 再生模型，并研究了这种独特愈合反应背后的细胞动力学。我们分别使用 Scleraxis (Scx) 和 Sonic Hedgehog (Shh) 对小鼠进行遗传谱系追踪，以分别绘制纤维环 (AF) 和髓核 (NP) 细胞的命运图。结果表明在新生儿而非成人中发生严重疝气损伤后功能性房颤再生。AF 再生由 Scx 谱系细胞介导，这些细胞失去 ScxGFP 表达并采用茎/祖细胞表型（Sca-1，第 3-14 天），增殖，然后在第 56 天再分化为产生 I 型胶原蛋白的 ScxGFP+ 环细胞。在新生儿修复过程中也短暂观察到非 Scx 谱系细胞，包括 Shh 谱系细胞、巨噬细胞和肌成纤维细胞；然而，到第 56 天，当环细胞再分化时不再检测到这些群体。总体而言，成人未发生修复。这些结果确定了一种令人兴奋的新生儿 AF 再生细胞机制，该机制主要由 Scx 谱系环细胞驱动。